US2523528A - N' (4-hydroxy-4-isoimidazol-2-yl)sulfonamides and their production - Google Patents

N' (4-hydroxy-4-isoimidazol-2-yl)sulfonamides and their production Download PDF

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US2523528A
US2523528A US86408A US8640849A US2523528A US 2523528 A US2523528 A US 2523528A US 86408 A US86408 A US 86408A US 8640849 A US8640849 A US 8640849A US 2523528 A US2523528 A US 2523528A
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hydroxy
weight
isoimidazol
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alpha
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US86408A
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Jonathan W Williams
Thurmond A Williamson
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EIDP Inc
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EI Du Pont de Nemours and Co
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    • CCHEMISTRY; METALLURGY
    • C07ORGANIC CHEMISTRY
    • C07DHETEROCYCLIC COMPOUNDS
    • C07D233/00Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings
    • C07D233/54Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having two double bonds between ring members or between ring members and non-ring members
    • C07D233/66Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having two double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
    • C07D233/88Nitrogen atoms, e.g. allantoin

Definitions

  • This invention relates to N(hydroxy-4-isoimidazol-Z-yl) sulfanilamides and their alkali metal salts and to methods for their preparation.
  • N(4 hydroxy-4-isoimidazol-2-yl)sulfanilamides of the invention are represented by the formula e anilamides of the inventionare easily formed by substitution of the alkali metal for the N-hydrogen atom on the sulfonamido group; such salts are valuable because of their solubility in water.
  • the compounds of the invention are prepared by the condensation of an aliphatic alpha-diketone with sulfaguanidine or its monohydrate, or with a benzene sulfonyl guanidine which con tains in the para position a substituent capable of being converted into an amino group.
  • Typical suitable alpha-diketones are glyoxal, pyruvaldehyde, biacetyl, 2,3- pentanedione, 2 methyl 3,4 pentanedione, alpha-oxo-butyraldehyde, alpha-oxo-valeraldehyde, 2,3 hexanedione, 2,2-dimethyl-3,4,-pentanedione, 3,4 hexanedione, 2,5 dimethyl-3,4- hexanedione, 2,2,5 trimethyl-3,4-hexanedione, and 5-methyl-2,3-hexanedione.
  • the condensation reaction between sulfaguanidine and the alpha-diketone is most readily carried out in the presence of a solvent and is facilitated by the use of a small amount of a condensin agent.
  • Sulfuric acid is a satisfactory condensing agent.
  • N (4 hydroxy-4-isoimidazol-2-yl)sulfanilamides of the invention are fine-crystalline, high-melting, powdered solids, insoluble in the common low molecular weight organic solvents but soluble in aqueous alkali.
  • the alkali metal salts of the compounds are prepared by heating a suspension of the powdered sulfonamide in a solvent such as methanol in the presence of an excess of an alkali metal alkoxide such as sodium methoxide.
  • the alkali metal salts are-solid powders, soluble in water, very slightly soluble in the lower alcohols, and insoluble in the common hydrocarbon solvents.
  • the compounds of the present invention are particularly valuable as intermediates for the preparation of dyestuffs. They may also be used as insecticides, fungicides, and bactericides and may be useful for therapeutic purposes, and as intermediateproducts in the manufacture of therapeutically active substances.
  • a water-insoluble, reddish-orange dyestuff suitable for the coloring of acetate rayon fabrics is obtained from the compound of Example I by first reacting the compound of Example I with sodium nitrite in a cold-acidic suspension of the compound to form the diazo salt and then coupling this salt with alpha-naphthol.
  • a deep red-colored, water-soluble, wool dye is obtained by coupling the diazo salt of the compound of Example I with 1-naphthylamine-4-sulfonic acid.
  • a yellow, water-insoluble, cellulose acetate dye is obtained by coupling alpha-naphthol with the diazo salt of the compound of Example III.
  • EXAMPLE IV A mixture of 10 parts by weight of sulfaguanidine, 6 parts by weight of 5-methyl-2,3-hexanedione, 300 parts by weight of glacial acetic acid and 0.5 part by weight of concentrated sulfuric acid are heated at about 90 C. for one hour. The mixture is cooled and filtered to give 12 parts by Weight of N(4-hydroXy-4-isobuty1- 5 methyl 4-isoimidazol-2-yl)sulfanilamide, a light tan crystalline solid, M. P. 272-275 C. dec.
  • Brick red is the color of the dyestuff obtained by diazotizing the compound of Example IV with sodium nitrite and coupling the resulting diazo salt with alpha-naphthol.
  • alkali metal salts where R and R are selected from the class consisting of hydrogen and alkyl.

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  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)

Description

Patented Sept. 26, 1950 N' (4-HYDROXY-4-ISOIM'IDAZOL-2-YL) SUL- FONAMIDES AND THEIR PRODUCTION Jonathan W. Williams, Claymont, and Thurmond A. Williamson, Arden, DeL, assignors to E. I. du Pont de Nemours & Company, Wilmington, DeL, a corporation of Delaware No Drawing. Application April 8, 1949,
' Serial No. 86,408
(01. zen-ease 2 Claims. 1
This invention relates to N(hydroxy-4-isoimidazol-Z-yl) sulfanilamides and their alkali metal salts and to methods for their preparation.
The N(4 hydroxy-4-isoimidazol-2-yl)sulfanilamides of the invention are represented by the formula e anilamides of the inventionare easily formed by substitution of the alkali metal for the N-hydrogen atom on the sulfonamido group; such salts are valuable because of their solubility in water.
The compounds of the invention are prepared by the condensation of an aliphatic alpha-diketone with sulfaguanidine or its monohydrate, or with a benzene sulfonyl guanidine which con tains in the para position a substituent capable of being converted into an amino group.
The alpha-diketones used in the preparation salt of the N (4-hydroxy lisoimidazol-2-yl) sulfof the compounds of the invention are represented by the formula RG=O R'J1=O where R and R are hydrogen or alkyl; preferably the alkyl is loweralkyl, that is 1 to 5 car bon atoms inclusive. Typical suitable alpha-diketones are glyoxal, pyruvaldehyde, biacetyl, 2,3- pentanedione, 2 methyl 3,4 pentanedione, alpha-oxo-butyraldehyde, alpha-oxo-valeraldehyde, 2,3 hexanedione, 2,2-dimethyl-3,4,-pentanedione, 3,4 hexanedione, 2,5 dimethyl-3,4- hexanedione, 2,2,5 trimethyl-3,4-hexanedione, and 5-methyl-2,3-hexanedione.
The condensation reaction between sulfaguanidine and the alpha-diketone is most readily carried out in the presence of a solvent and is facilitated by the use of a small amount of a condensin agent. Sulfuric acid is a satisfactory condensing agent.
The N (4 hydroxy-4-isoimidazol-2-yl)sulfanilamides of the invention are fine-crystalline, high-melting, powdered solids, insoluble in the common low molecular weight organic solvents but soluble in aqueous alkali. I
The alkali metal salts of the compounds are prepared by heating a suspension of the powdered sulfonamide in a solvent such as methanol in the presence of an excess of an alkali metal alkoxide such as sodium methoxide. The alkali metal salts are-solid powders, soluble in water, very slightly soluble in the lower alcohols, and insoluble in the common hydrocarbon solvents.
The compounds of the present inventionare particularly valuable as intermediates for the preparation of dyestuffs. They may also be used as insecticides, fungicides, and bactericides and may be useful for therapeutic purposes, and as intermediateproducts in the manufacture of therapeutically active substances.
The invention will be more readily understood by reference to the followin examples which illustrate typical compounds of the invention, methods for their preparation, and their use.
EXAMPLE I N'(4 ethyl-4-hydro:ty-5-methyl-4-isoimidazol- Z-yl) sulfam'lamide 5 parts by weight of 2,3-pentanedione is added to a solution of 10 parts by weight of sulfaguanidine monohydrate in 300 parts b weight of ethanol. 0.1 part by weight of concentrated sulfuric acid is added to the solution and the liquid is heated under reflux for 30 minutes. The mass is then cooled and filtered. There is obtained 13 parts by weight of yellow-colored v crystalline N (4 ethyl-4-hydroxy-5-methyl-4- isoimidazol-Z-yl)sulfanilamide, melting at 222- A water-insoluble, reddish-orange dyestuff suitable for the coloring of acetate rayon fabrics is obtained from the compound of Example I by first reacting the compound of Example I with sodium nitrite in a cold-acidic suspension of the compound to form the diazo salt and then coupling this salt with alpha-naphthol. A deep red-colored, water-soluble, wool dye is obtained by coupling the diazo salt of the compound of Example I with 1-naphthylamine-4-sulfonic acid.
EXAMPLE II N (4,5-dimethyl-4-hydroxy-4-isoimidazol-2- yl) sulfanilamide 216 parts by weight of sulfaguanidine monohydrate and 80 parts by weight of biacetyl in 600 parts by weight of glacial acetic acid is heated at 90 C. for 30 minutes. The mixture is cooled and filtered to give 208 parts by weight of crystalline N'(4,5 dimethyl-4-hydroxy-4-isoimidazol-2-yl)sulfanilamide as a pale tan powder melting at 260-265" C.
By diazotizing the compound of Example II and coupling it with alpha-naphthol, a yellowbrown dyestuff is obtained; coupling the diazotized compound with 1-naphthylamine-4-sulfonic acid gives a deep red product.
EXAMPLE III N (4-methyl-el-hydroxy-4-isoimida2ol- 2-yl) sulfam'lamide parts by weight of sulfaguanidine monohydrate is dissolved in 100 parts by weight of glacial acetic acid and 10 parts by weight of 30.4% aqueous pyruvic aldehyde is added thereto. The mixture is heated at 60 C. for minutes, cooled and filtered. There is obtained 11 parts by weight of a brown crystalline solid melting at 245 C. with gross decomposition.
A yellow, water-insoluble, cellulose acetate dye is obtained by coupling alpha-naphthol with the diazo salt of the compound of Example III.
EXAMPLE IV A mixture of 10 parts by weight of sulfaguanidine, 6 parts by weight of 5-methyl-2,3-hexanedione, 300 parts by weight of glacial acetic acid and 0.5 part by weight of concentrated sulfuric acid are heated at about 90 C. for one hour. The mixture is cooled and filtered to give 12 parts by Weight of N(4-hydroXy-4-isobuty1- 5 methyl 4-isoimidazol-2-yl)sulfanilamide, a light tan crystalline solid, M. P. 272-275 C. dec.
Brick red is the color of the dyestuff obtained by diazotizing the compound of Example IV with sodium nitrite and coupling the resulting diazo salt with alpha-naphthol.
EXAMPLE V Sodium salt of N '(4,5-dimethyl-4-hydroxy- 4-isoz'midazoZ-2-yl) sulfam'lamide A mixture of 5 parts by weight of N (4,5-dimethyl 4 hydroxy-4-isoimidazol-2-yl) sulfanil- AMONH,
and then alkali metal salts, where R and R are selected from the class consisting of hydrogen and alkyl.
2. A process for the manufacture of a N (4-hydroxy 4-isoimidazol-2-yl) sulfanilamide which comprises heating an alpha-diketone represented by the formula R'-J=O where R and R are from the class consisting of hydrogen and alkyl, with sulfaguanidine to effect condensation of the two compounds.
JONATHAN W. WILLIAMS. THURMOND A. WILLIAMSON.
REFERENCES CITED The following references are of record in the file of this patent:
UNITED STATES PATENTS Number Name Date 2,357,249 Anderson Aug. 29, 1944. 2,435,002 Hartmann et al. Jan. 27, 1948 FOREIGN PATENTS Number Country Date 521,821 Great Britain May 31, 1940 OTHER REFERENCES Ganapathi, Proceedings Indian Academy of Science, vol. 13 (1941), pages 316-389.

Claims (1)

1. A COMPOUND SELECTED FROM THE GROUP CONSISTING OF N''(4-HYDROXY-4-ISOIMIDAZOL-2-Y)SULFANILAMIDES REPRESENTED BY THE FORMULA AND THEN ALKALI METAL SALTS, WHERE R AND R'' ARE SELECTED FROM THE CLASS CONSISTING OF HYDROGEN AND ALKYL.
US86408A 1949-04-08 1949-04-08 N' (4-hydroxy-4-isoimidazol-2-yl)sulfonamides and their production Expired - Lifetime US2523528A (en)

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Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US2858309A (en) * 1956-05-07 1958-10-28 Ciba Pharm Prod Inc New aminobenzene sulfonamide

Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
GB521821A (en) * 1938-11-28 1940-05-31 May & Baker Ltd The preparation of new therapeutically useful heterocyclic compounds
US2357249A (en) * 1942-02-10 1944-08-29 American Cyanamid Co Method of preparing sulphanilyl aryl guanidines
US2435002A (en) * 1942-01-30 1948-01-27 Ciba Pharm Prod Inc Process for the manufacture of para-aminobenzene-sulphonamidopyrimidines

Patent Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
GB521821A (en) * 1938-11-28 1940-05-31 May & Baker Ltd The preparation of new therapeutically useful heterocyclic compounds
US2435002A (en) * 1942-01-30 1948-01-27 Ciba Pharm Prod Inc Process for the manufacture of para-aminobenzene-sulphonamidopyrimidines
US2357249A (en) * 1942-02-10 1944-08-29 American Cyanamid Co Method of preparing sulphanilyl aryl guanidines

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US2858309A (en) * 1956-05-07 1958-10-28 Ciba Pharm Prod Inc New aminobenzene sulfonamide

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